Hemodialysis-induced leukopenia is a transient, acute decrease in granulocytes and monocytes that occurs during the first hour of hemodialysis using cellophane membranes. This phenomenon is attributed to complement activation by dialyzer cellophane, leading to granulocyte and monocyte entrapment in the pulmonary vasculature. During early dialysis, complement components C3 and factor B are converted in plasma as it passes through the dialyzer. Incubation of human plasma with dialyzer cellophane also causes C3 and factor B conversion, accompanied by depletion of total hemolytic complement and C3, but sparing of hemolytic C1. Reinfusion of cellophane-incubated plasma into rabbits results in selective granulocytopenia and monocytopenia, with granulocytes trapped in pulmonary vessels. The activated complement component responsible for leukostasis has a molecular weight of approximately 7,000–20,000 daltons and is generated in C2-deficient plasma, suggesting activation via the alternative pathway. The studies demonstrate that dialyzer cellophane induces complement activation, leading to pulmonary leukostasis and peripheral leukopenia in dialyzed patients. The mechanism involves complement activation by cellophane, which leads to granulocyte and monocyte sequestration in the pulmonary vasculature. The findings suggest that complement activation by dialysis is primarily through the alternative pathway. The transient nature of leukopenia is likely due to the progressive inability of cellophane membranes to activate complement during the dialysis process. These findings provide insights into the pathophysiology of hemodialysis-induced leukopenia and may have implications for understanding other clinical conditions involving complement activation.Hemodialysis-induced leukopenia is a transient, acute decrease in granulocytes and monocytes that occurs during the first hour of hemodialysis using cellophane membranes. This phenomenon is attributed to complement activation by dialyzer cellophane, leading to granulocyte and monocyte entrapment in the pulmonary vasculature. During early dialysis, complement components C3 and factor B are converted in plasma as it passes through the dialyzer. Incubation of human plasma with dialyzer cellophane also causes C3 and factor B conversion, accompanied by depletion of total hemolytic complement and C3, but sparing of hemolytic C1. Reinfusion of cellophane-incubated plasma into rabbits results in selective granulocytopenia and monocytopenia, with granulocytes trapped in pulmonary vessels. The activated complement component responsible for leukostasis has a molecular weight of approximately 7,000–20,000 daltons and is generated in C2-deficient plasma, suggesting activation via the alternative pathway. The studies demonstrate that dialyzer cellophane induces complement activation, leading to pulmonary leukostasis and peripheral leukopenia in dialyzed patients. The mechanism involves complement activation by cellophane, which leads to granulocyte and monocyte sequestration in the pulmonary vasculature. The findings suggest that complement activation by dialysis is primarily through the alternative pathway. The transient nature of leukopenia is likely due to the progressive inability of cellophane membranes to activate complement during the dialysis process. These findings provide insights into the pathophysiology of hemodialysis-induced leukopenia and may have implications for understanding other clinical conditions involving complement activation.